The Impact of Parental Longevity on Brain Health - and the Influence of Physical Functions and Genetics

家长津贴(R01AG062659) 特定目标：大脑、步态和认知衰退的轨迹和可改变的危险因素 在衰老和痴呆前期中 摘要： 在美国，大约35%的社区老年人存在临床步态异常， 步态加速下降会导致许多不利的身体和认知后果-- 包括跌倒、残疾、认知能力下降和痴呆症。这样的结果不仅减少了 受影响的个人及其家人和朋友的生活质量，但也会导致健康水平的提高 护理费用。我们的研究旨在了解大脑老化、步态 衰退、认知衰退和痴呆症--并将指导未来对 在衰老和早期痴呆中保持步态和认知。步态加速下降与 认知衰退、阿尔茨海默病和相关痴呆的风险增加(1-9)。一个 对这种联系的常见解释是，步态和认知依赖于共享的神经 受正常和痴呆症相关老化影响的底物(10-13)。然而，神经 将步态、认知和痴呆症联系在一起的底物还没有被很好地理解。更好地理解 这些神经底物-以及它们如何受到潜在的可修改的风险因素的影响 痴呆症，如糟糕的社会网络或支持(14，15)--对于发展有效的 老年和早期痴呆患者维持步态和认知能力的治疗方法。我们建议比较一下 老年人脑功能和结构改变、步态下降和认知能力下降的轨迹 认知正常的成年人，以及处于认知衰退早期阶段的人。 目标1：比较功能性和结构性脑老化、步态下降和 认知能力下降。 H1a：脑功能和结构改变，主要发生在辅助运动区、岛和 PFC，先于步态和认知衰退(比步态更陡峭或变化点更早)。 H.1b：与步态和认知衰退相关的功能性脑变化先于结构性脑 改变。 目的2：研究MCR对脑功能和结构改变、步态和运动的影响。 认知能力下降。 H.2：大脑功能和结构变化的轨迹，主要是辅助运动区， 在有MCR的患者中，脑岛和PFC的变化点比无MCR的患者更陡峭/更早。 目标3：研究社会网络在大脑功能和结构变化中的作用， 步态和认知能力下降。 H.3：大脑功能和结构变化的轨迹，主要是在脑岛和PFC，步态和 拥有较小社交网络的人认知能力下降幅度更大/变化点更早 大型社交网络。

Parent Grant (R01AG062659) Specific Aims: Trajectories and modifiable risk factors of brain, gait, and cognitive decline in aging and pre-dementia ABSTRACT: Clinical gait abnormalities are present in about 35% of community-dwelling older adults in the US, and accelerated gait decline is associated with many adverse physical and cognitive outcomes - including falls, disability, cognitive decline, and dementia. Such outcomes not only reduce the quality of life of affected individuals, their families, and friends, but also leads to increased health care costs. Our research aims to understand the interrelationship between brain aging, gait decline, cognitive decline, and dementia – and will guide future development of interventions for maintaining gait and cognition in aging and early dementia. Accelerated gait decline is associated with an increased risk for cognitive decline, Alzheimer’s disease, and related dementias (1-9). A common explanation of such associations is that gait and cognition rely on shared neural substrates that are affected by both normal and dementia-related aging (10-13). Yet, the neural substrates that link gait, cognition, and dementia are not well-understood. A better understanding of these neural substrates – and how they are influenced by potentially modifiable risk factors of dementia such as poor social networks or support (14, 15) – is important for developing effective therapies for maintaining gait and cognition in aging and early dementia. We propose to compare trajectories of functional and structural brain changes, gait decline and cognitive decline in older adults who are cognitively normal, and those in the early stages of cognitive decline. Aim 1: Compare trajectories of functional and structural brain aging, gait decline and cognitive decline. H.1a: Functional and structural brain changes, mainly in supplementary motor area, insula, and PFC, precede (are steeper or have earlier change points than) gait and cognitive decline. H.1b: Functional brain changes related to gait and cognitive decline precede structural brain changes. Aim 2: Examine the influence of MCR on functional and structural brain changes, gait, and cognitive decline. H.2: Trajectories of functional and structural brain changes, mainly in supplementary motor area, insula, and PFC, are steeper/have earlier change points in those with MCR than non-MCR. Aim 3: Examine the role of social networks on functional and structural brain changes, gait, and cognitive decline. H.3: Trajectories of functional and structural brain changes, mainly in insula and PFC, gait and cognitive decline are steeper/have earlier change points in those with small social networks than large social networks.